HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

Gene therapy approaches in the non-human primate model of Parkinson's disease.

The field of gene therapy has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using vectors carrying genes to further modify basal ganglia circuits of interest. It is expected that these approaches will ultimately induce a therapeutic potential being sustained by gene-induced changes in brain circuits. Among others, at present, it is technically feasible to use viral vectors to (1) achieve a controlled release of neurotrophic factors, (2) conduct either a transient or permanent silencing of any given basal ganglia circuit of interest, (3) perform an in vivo cellular reprogramming by promoting the conversion of resident cells into dopaminergic-like neurons, and (4) improving levodopa efficacy over time by targeting aromatic L-amino acid decarboxylase. Furthermore, extensive research efforts based on viral vectors are currently ongoing in an attempt to better replicate the dopaminergic neurodegeneration phenomena inherent to the progressive intraneuronal aggregation of alpha-synuclein. Finally, a number of incoming strategies will soon emerge over the horizon, these being sustained by the underlying goal of promoting alpha-synuclein clearance, such as, for instance, gene therapy initiatives based on increasing the activity of glucocerebrosidase. To provide adequate proof-of-concept on safety and efficacy and to push forward true translational initiatives based on these different types of gene therapies before entering into clinical trials, the use of non-human primate models undoubtedly plays an instrumental role.

Update on Crohn's disease: a polymorphic entity.

Crohn's disease is a chronic transmural inflammatory disease that most commonly affects the intestinal wall, but may also occur in any part of the gastrointestinal tract; its incidence is higher in industrialized countries, urban areas and upper socioeconomic classes. Various environmental risk factors have been associated with the pathogenesis of Crohn's disease and possible infectious agents (viruses, bacteria, yeasts) have also been considered. However, none of these factors alone leads to the development of the disease, which may occur only when there is a genetic predisposition and/or an abnormal function of the intestinal immune system. Histopathology demonstrates mucosal hyperemia, with small superficial ulcers in mild forms of the disease; in moderate-to-severe forms, serpiginous ulcerations demarcating areas of edematous mucosa produce the characteristic "cobblestone" appearance. The earliest microscopic lesions appear as neutrophil-mediated cryptic damage, with the formation of focal cryptic abscesses and granulomas throughout the layers of the intestinal wall. In addition to weight loss, patients mainly refer chronic diarrhea and recurrent right iliac fossa abdominal pain. Extraintestinal manifestations include ocular or articular complications. There are several drugs classes available for treating Crohn's disease, but the therapeutic approach depends on the clinical picture and differs from patient to patient. The broad clinical and the histopathological features of Crohn's disease make it a highly polymorphic entity. Diagnostic tests and a thorough knowledge of its various aspects are essential for guiding diagnosis and treatment.

Prevalence and risk factors for acute stress disorder in female victims of sexual assault.

Sexual assault is one of the most traumatic events a person can experience. Despite this, information regarding the risk factors associated with the development of Acute Stress Disorder (ASD) in sexual assault victims is scarce. A follow-up prospective cohort study was designed to examine the prevalence and risk factors of ASD in women exposed to a recent sexual assault. A total of 156 women were treated at the Emergency Department of a university general hospital shortly after sexual assault. Sociodemographic, clinical and sexual assault-related variables were collected. The Acute Stress Disorder Interview was used to estimate the prevalence of ASD at three weeks post-SA. From the 156 victims, 66.6% (N = 104) met ASD diagnosis using DSM-5 criteria, whereas 59.6% (N = 93) met ASD diagnosis using DSM-IV criteria. The risk factors associated with the development of ASD were nationality, psychiatric history, peritraumatic dissociation and type of assault. In conclusion, the prevalence of ASD in female victims of recent sexual assault was high, affecting approximately two thirds of them. The recognition of the risk factors associated with ASD development, like peritraumatic dissociation or type of assault, may aid in the prompt detection of vulnerable women that require early and specific interventions shortly after trauma.

Assessing health effects of environmental contaminants by molecular markers. Studies on methylmercury and polychlorinated biphenyls as examples of translational research in environmental toxicology.

Evaluating the human effects of combinations of neurotoxicants is extremely difficult. Parallel studies correlating exposure parameters and "surrogate" indicators of neural cell function may represent a promising strategy. Molecular markers such as cholinergic muscarinic receptors (MRs) and monoamine oxidase activity (MAO-B) are expressed not only in brain but also in peripheral blood cells. Measurements of MRs and MAO-B in these easily accessible matrices can provide valuable information on early sub-clinical effects of drugs and chemicals in the CNS. In this paper, examples of application of lymphocyte-MRs and platelet-MAO-B as surrogate markers of CNS function in humans are described. They include (i) neuroepidemiological studies examining 7-year-old members of a birth-cohort at the Faroe-Islands prenatally exposed to elevated concentrations of methylmercury (MeHg) and polychlorinated biphenyls; (ii) clinical investigations in a series of unmedicated children with Attention-Deficit/Hyperactivity Disorder (ADHD). The neurochemical markers were examined in association with exposure indicators and neuropsychological tests (Faroe Islands Study) or with specific disease symptoms (ADHD children). Studies of this type have produced valuable information on subclinical responses to low/moderate perinatal exposures to MeHg and/or PCBs, and in addition further supported the applicability of these biomarkers in children with subtle neuropsychiatric disorders. Additional studies investigated the ability of MeHg and/or PCBs to modify the expression of genes codifying for the MR subtypes in rat offspring cerebellum at distinct developmental stages. The results demonstrated persistent gender- and age-related differences in MR density and their associated gene expression pathways. Studies on pathways and metabolic networks involved in developmental toxicity may contribute to elucidate the mode of action of environmental pollutant mixtures and also considerably impact on the risk assessment process.

Squamous cell carcinoma over pilonidal chronic disease. A new therapeutic approach.

INTRODUCTION: Pilonidal sinus is a very common disease. Malignant transformation occurs in 0,1% of patients. We present a case of squamous cell carcinoma arised from recurrent pilonidal disease, managed by multimodal treatment. PRESENTATION OF CASE: We present a 70-year-old man with chronic pilonidal sinus. Inflammation had worsened in previous months and exploration revealed a large ulcerative mass which biopsy showed a squamous cell carcinoma. CT scan and MRI imaging showed tumoral invasion of the coccyx and both gluteus major muscles. Neoadjuvant radiotherapy, chemotherapy as radiosensitizer and surgery with intraoperative radiotherapy was decided in the multidisciplinary tumor committee. Post neoadjuvant therapy MRI showed partial response with a decrease of the mass but persistence of the coccyx infiltration. Surgery consisted in en-bloc resection of the tumor with presacral tissues, coccyx and partial gluteal resection. Intraoperative radiotherapy was administered over the sacrum and in the bed of the coccyx resection. One week later, reconstructive surgery was practiced using a latissimus dorsi free flap, advancement of gluteal flaps and skin graft. Histological examination showed no residual tumor. The patient is currently asymptomatic and he has a satisfactory quality of life. DISCUSSION: Although squamous cell carcinoma is rare, it must be suspected in patients with recurrent pilonidal disease. Diagnosis is done by histological examination of biopsies. This type of tumors have a high local recurrence rate. CONCLUSION: We propose a multimodal treatment that includes neoadjuvant radiotherapy and chemotherapy as radiosensitizer and surgery plus intraoperative radiotherapy with the aim to decrease local recurrence rate.

Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study.

OBJECTIVE: Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. METHODS: 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). RESULTS: The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett's oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett's oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett's oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. CONCLUSIONS: GORD is common in Italy, but the prevalence of Barrett's oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett's oesophagus often have no reflux symptoms.

Pulmonary and hepatic effects after low dose exposure to nanosilver: Early and long-lasting histological and ultrastructural alterations in rat.

Although environmental airborne silver nanoparticles (AgNPs) levels in occupational and environmental settings are harmful to humans, the precise toxic effects at the portal entry of exposure and after translocation to distant organs are still to be deeply clarified. To this aim, the present study assessed histopathological and ultrastructural alterations (by means of H&E and TEM, respectively) in rat lung and liver, 7 and 28 days after a single intratracheal instillation (i.t) of a low AgNP dose (50 microg/rat), compared to those induced by an equivalent dose of ionic silver (7 microg AgNO3/rat). Lung parenchyma injury was observed acutely after either AgNPs or AgNO3, with the latter compound causing more pronounced effects. Specifically, alveolar collapse accompanied by inflammatory alterations and parenchymal fibrosis were revealed. These effects lasted until the 28th day, a partial pulmonary structure recovery occurred, nevertheless a persistence of slight inflammatory/fibrotic response and apoptotic phenomena were still detected after AgNPs and AgNO3, respectively. Concerning the liver, a diffuse hepatocyte injury was observed, characterized by cytoplasmic damage and dilation of sinusoids, engulfed by degraded material, paralleled by inflammation onset. These effects already detectable at day 7, persisting at the 28th day with some attenuations, were more marked after AgNO3 compared to AgNPs, with the latter able to induce a ductular reaction. Altogether the present findings indicate toxic effects induced by AgNPs both at the portal entry (i.e. lung) and distant tissue (i.e. liver), although the overall pulmonary damage were more striking compared to the hepatic outcomes.

Comparative HPLC and ELISA studies for CDT isoform characterization in subjects with alcohol related problems. Prospective application in workplace risk-prevention policy.

Serum carbohydrate-deficient transferrin (CDT) is the most specific marker of chronic alcohol abuse so far. The performance of commercial HPLC over the ELISA method for measurement of CDT was evaluated on a series of 105 serum samples obtained from subjects referred to the Toxicology Laboratory of Salvatore Maugeri Hospital for alcohol-related problems. Compared to ELISA, HPLC analysis was more valuable for determining alcohol-related patterns of CDT isoforms and quantifying serum levels of disialotransferrin that better reflect chronic heavy drinking. Other significant advantages of the HPLC method included reproducible separation and easier detection of glycoform types and genetic transferrin variants that are known to cause falsely high or low results in sera examined by immunoassay. Current scientific evidence indicates that disialotransferrin is the target analyte for CDT determination and HPLC the current CDT analysis reference method. Systematic studies for early assessment of excessive alcohol intake or abuse of alcoholic substances in workers are recommended by the Italian legislation in accordance with the European Alcohol Action Plan (EAAP) launched by the WHO Regional Committee for Europe. These studies are advisable given their potential role in preventing negative effects of alcohol abuse in workplace. A research strategy combining CDT and other laboratory markers with questionnaire and physician interview is recommended for examining subjects with alcohol related problems and the diagnosis of alcoholism. This approach can be applied for alcohol abuse in workplace surveillance.

Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid.

BACKGROUND: The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined. AIM: To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta. MATERIALS AND METHODS: Forty-three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real-time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data. RESULTS: Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups. CONCLUSIONS: Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.

Monoamine receptors and immature cerebellum cytoarchitecture after cisplatin injury.

The experimental model of cisplatin treatment provides the opportunity to identify the precise function of the neurotransmitters in some crucial events of brain development, and their interactions or modulatory roles. The serotonin and noradrenaline monoamines influence the formation of the cerebellar cortex circuitry. In this study we found changes in the expression of the serotonin and noradrenaline receptors after a single injection of cisplatin in 10-day-old rats. The growth of Pc dendrites was early altered in lobules VI-VIII of cerebellum vermis. In these lobules, at postnatal day (PD) 17, the cisplatin-induced increase of the serotoninergic receptor 5-HT2AR, a factor that inhibits Pc dendrite growth by acting post-synaptically, occurred in all cerebellar layers, suggesting also alteration of granule cell proliferation and migration. The decreased labelling of beta l adrenergic receptor (beta1AR) in the soma of some Pc at PD11 can be correlated with the altered expression of glutamate receptors and GAD65 (glutamic acid decarboxylase) of and on Pc we have previously described [Pisu, M.B., Guioli, S., Conforti, E., Bernocchi, G., 2003. Signal molecules and receptors in the differential development of cerebellum lobules. Acute effects of cisplatin on nitric oxide and glutamate system in Purkinje cell population. Dev. Brain Res. 145, 229-240; Pisu, M.B., Roda, E., Avella, D., Bernocchi, G., 2004. Developmental plasticity of rat cerebellar cortex after cisplatin injury: inhibitory synapses and differentiating Purkinje neurons. Neuroscience 129, 655-664]. Moreover, beta1AR seems to be the key factor in the cerebellar reorganization between PD17 and PD30. The expression of this receptor was maintained in the molecular layer (ML), in particular in the inhibitory interneurons, despite their different distributions. The labelling of 5-HT1AR in the ML areas lacking Pc dendrite branches could contribute to the recovery phase of the cerebellar cytoarchitecture in cisplatin-treated rats. In general these findings should be taken into consideration in therapeutic interventions for developmental CNS disorders with a morphological basis.

A statistical model predicting high hepatocyte proliferation index and the risk of developing hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Incidence of hepatocellular carcinoma in hepatitis C virus-related cirrhosis is 4% per year. Although cost-effective, current screening could be improved. AIM: To develop a statistical model including non-invasive parameters able to identify patients at high risk of developing hepatocellular carcinoma. METHODS: One hundred and fifty-eight patients (73F:85M) with compensated chronic hepatitis C virus liver disease underwent evaluation, including argyrophilic nucleolar organizer regions proliferation index, and were followed up for 56.18 +/- 1.44 months. RESULTS: Fifty-six patients had chronic hepatitis without cirrhosis and low argyrophilic nucleolar organizer regions proliferation index (< or =25%), 65 had hepatitis C virus-related cirrhosis and low argyrophilic nucleolar organizer regions proliferation index and 37 had hepatitis C virus-related cirrhosis and high argyrophilic nucleolar organizer regions proliferation index (>25%). Groups were similar for gender and viral genotype distribution. None of the patients with chronic hepatitis without cirrhosis developed hepatocellular carcinoma, compared with 6.1% of low argyrophilic nucleolar organizer regions proliferation index and 30.6% of high argyrophilic nucleolar organizer regions proliferation index (P = 0.002). By multivariable logistic regression analysis, the following parameters were independently associated with hepatocellular carcinoma development and used for the development of the statistical model: platelets (OR 0.98), gamma-globulins (OR 0.111), alanine aminotransferase/aspartate aminotransferase ratio (OR 0.07), serum ferritin (OR 1.0) and ultrasonographic pattern (coarse OR 2.9, coarse nodular OR 10.12). The statistical model properly allocated 95.9% of patients with low argyrophilic nucleolar organizer regions proliferation index and 72.2% of patients with high argyrophilic nucleolar organizer regions proliferation index. CONCLUSIONS: The model, to be validated in large prospective studies, may help tailoring screening according to the risk of hepatocellular carcinoma development.

Cost-effectiveness of different diagnostic strategies to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough in Italy.

BACKGROUND: Chronic persistent cough is a common and disabling disorder and gastro-oesophageal reflux disease is considered to be the third leading cause, after asthma and postnasal drip. Therefore, patients with unexplained chronic persistent cough usually undergo a stepwise evaluation to establish the existence of a reflux disease. AIM: To identify the most cost-effective diagnostic approach to assess gastro-oesophageal reflux disease in patients with unexplained chronic persistent cough. METHODS: Direct and indirect costs associated with six diagnostic strategies using 24-h oesophageal pH-metry, oesophago-gastroduodenoscopy and the proton pump inhibitors test in different sequences, were evaluated using a decision tree model. If the first test was positive, the diagnostic work-up was stopped, if negative the patient proceeded to the second test, and so on. Clinical data from an observational prospective trial conducted in 51 patients with unexplained chronic persistent cough were used in the economic model. RESULTS: All six strategies had the same clinical effectiveness (78.4%). The diagnostic work-up with the lowest cost was the proton pump inhibitors test followed by pH-metry and then oesophago-gastroduodenoscopy with a total cost of euro 211.08 (direct euro 142.93, indirect euro 68.15). CONCLUSIONS: This study shows that the lowest cost is the strategy where proton pump inhibitors test is performed as first investigation. Implementation of this diagnostic work-up may lead to cost savings in the management of patients with chronic persistent cough.

Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients.

AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR). METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR. RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t(1/2)) than CTR (P < 0.0044) at baseline; after UDCA, t(1/2) significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR. CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation.

Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication.

Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1-4.5; UHg 0.1-4.5), associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0-16.0). At t1 (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA chelating therapy ending), gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.) and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes). Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

Pathophysiology and pharmacotherapy of cholelithiasis.

Several factors are involved in the development of gallstone formation: formation of supersaturated bile; nucleation; formation, retention and adhesion of cholesterol crystals and eventually stone growth. The dynamics of the gallbladder may play a key role in the overall process. The pathophysiologic theory of cholesterol gallstone formation and the knowledge of their physico-chemical properties support the modern concept of gallstone therapy. Chenodeoxycholic and ursodeoxycholic have been widely used as cholesterol gallstone dissolving agents and evaluated in terms of efficacy and safety.

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels.

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Tissue damage after acute intoxication by polychlorinated biphenyls in cockroaches.

It is common knowledge that polychlorinated biphenyls (PCBs) represent a serious threat to the health of both vertebrates and invertebrates. As far as the former are concerned, especially as regards human beings, a broad literature describes the direct and indirect effects induced by the PCBs on their systems and organs. Among invertebrates, the information available is mostly related to arthropods and is, however, very scarce. The aim of this work was to evaluate the effects of polychlorinated biphenyls (PCBs) on tissues and organs of individuals belonging to a species of Blattaria (Blattella germanica) treated with various doses of this toxic material. The pathologies found became more serious as the dosage increased and were present throughout the entire digestive system, in the fat body and in the male gonads: in these areas cell and tissue breakdown and severely damaged spermiogenesis were observed. In particular, the testes, Malpighian tubules and fat body accumulated an amorphous basophilic PAS-positive substance. Furthermore, the NOS-dependent NADPH diaphorase activity pattern in the retina and optic lobes was more evident in the treated than in the control insects.

[Use of intraoperative lymphoscintigraphy in doubtful cases of sentinel node detection]. / Uso de la linfogammagrafía intraoperatoria en los casos dudosos de detección del ganglio centinela.

Lymphoscintigraphy is a widely accepted method used to detect selectively the sentinel node in malignant melanoma. This is the case report of a patient who was operated on for an inguinal melanoma and who was referred to the Nuclear Medicine Section for preoperative lymphoscintigraphy. There were technical problems for sentinel node detection due to the proximity of injection points. We aimed to know the possibility to perform an intraoperative lymphoscintigraphy as a valid and useful technique in cases as this one.

Hepatic steatosis in obese patients: clinical aspects and prognostic significance.

Non-alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury-related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin-sensitizing agents, anti-oxidants or cytoprotective drugs may be useful, but there is no evidence-based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.